Generation of Biochemical Energy Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015
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- Slide 1
- Generation of Biochemical Energy Dr. Mamoun Ahram Biochemistry
for Nursing Summer 2015
- Slide 2
- PART (1): NOTES ON ENERGY
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- How do we get energy? We generate energy from the oxidation of
biomolecules made mainly of carbon, hydrogen, and oxygen. The end
products are carbon dioxide, water, and energy:
- Slide 4
- Acetyl Coenzyme A (acetyl CoA) The principal food molecules
lipids, proteins, and carbohydrates are broken down by separate
pathways into a common end-product called acetyl coenzyme A.
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- Energy-producing pathways Acetyl CoA enters the central, final
pathways to yield usable energy.
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- ENERGY AND LIFE
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- Energy: from start to end Chemical energy is stored in chemical
bonds Energy can be converted from one form to another but can be
neither created nor destroyed.
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- Conditions related to energy Energy must be released from food
gradually. Energy must be stored in accessible forms (fast and
easy). Release of energy from storage must be controlled so that it
is available exactly when and where it is needed. Just enough
energy must be released as heat to maintain constant body
temperature. Energy in a form other than heat must be available to
drive chemical reactions that are not favorable.
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- ENERGY AND BIOCHEMICAL REACTIONS
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- Types of energy There are two forms of energy potential -
capacity to do work (stored) kinetic - energy of motion Potential
energy is more important in the study of biological or chemical
systems.
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- Free energy (G) All molecules have potential energy within
them. Molecules have their own potential energy stored in the bonds
connecting atoms in molecules. This is known as free energy or G IN
biochemistry. free energy indicates the energy of a chemical that
is available for useful work
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- GG In any given reaction (reactants products), the difference
between the free energy values between reactants and products
(free-energy change G) is defined by G = G products G
reactants
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- What does it mean? G = G products G reactants If G is negative
(G products is less than G reactants ), energy is not needed to
drive the reaction but released, making the reaction spontaneous
(the reaction is called exergonic). If G is positive (G products is
more than G reactants ), energy is needed, making the reaction not
spontaneous (the reaction is called endergonic). If G is zero, both
forward and reverse reactions occur at equal rates; the reaction is
at equilibrium.
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- Favorable vs. unfavorable reactions d d The larger the positive
free-energy change, the greater the amount of energy that must be
added to convert the reactants to products.
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- How do enzymes accelerate reactions? Enzymes accelerate how
quickly this equilibrium is reached. Enzymes lower the activation
energy.
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- G values and signs The free-energy change switches sign for the
reverse of a reaction, but the value does not change. Energy is
stored in the products of an overall endergonic reaction pathway.
This stored energy is released as needed in an overall exergonic
reaction pathway that regenerates the original reactants.
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- CELLS AND THEIR STRUCTURE
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- Organelles inside cells Eukaryotic cells are made of organelles
(small, functional units that perform specialized tasks) The
organelles are surrounded by the fluid part of the cytoplasm, the
cytosol, which contains electrolytes, nutrients, and many enzymes,
all in aqueous solution.
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- The mitochondria The mitochondria (one is mitochondrion)
responsible for energy production. It produces 90% of ATP. The
number of mitochondria is greatest in eye, brain, heart, and muscle
cells, where the need for energy is greatest.
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- Structure of mitochondrion A mitochondrion is composed of a
smooth outer membrane and a folded inner membrane The space
enclosed by the inner membrane is the mitochondrial matrix.
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- Metabolic pathways Catabolism Metabolic reaction pathways that
break down food molecules and release biochemical energy. Anabolism
Metabolic reactions that build larger biological molecules from
smaller pieces.
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- How do metabolic pathways look like? Metabolism: All chemical
reactions that occur in an organism. Such pathways may be: linear
(that is, the product of one reaction serves as the starting
material for the next); cyclic (a series of reactions regenerates
one of the first reactants) spiral (the same set of enzymes
progressively builds up or breaks down a molecule)
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- Catabolic pathways
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- STRATEGIES OF METABOLISM
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- Structure of adenosine triphosphate
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- Hydrolysis of ATP Removal of one of the phosphate groups groups
from ATP by hydrolysis gives adenosine diphosphate (ADP). Note that
the ATP ADP reaction is exergonic (it releases chemical energy that
is stored in the bonds)
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- Strategy 1: ATP and Energy Transfer Biochemical energy is
gathered from exergonic reactions that produce ATP. The ATP goes to
where energy is needed inside the cell, and ATP hydrolysis releases
the energy for whatever energy- requiring work.
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- Why is ATP a favorable energy carrier? One: its synthesis and
hydrolysis is slow and enzymatically catalyzed (under regulation)
Two: it has intermediate value of the free energy of hydrolysis
relative to other high-energy compounds
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- Strategy 2: coupling reactions Energy stored in one chemical
compound is transferred to other compounds. How? Couple an
energetically unfavorable reaction to with an energetically
favorable reaction so that the overall energy change for the two
reactions is favorable. Note: the phosphoryl group is transferred
directly from ATP to glucose without the intermediate formation of
HPO 3 -
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- Synthesis of ATP from ADP Coupled reactions are written like
this:
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- Strategy 3: use of oxidized and reduced coenzymes Many
metabolic reactions are therefore oxidation reduction reactions,
which means that a steady supply of oxidizing and reducing agents
must be available. To deal with this requirement, a few coenzymes
cycle continuously between their oxidized and reduced forms
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- Examples of coenzymes
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- Oxidation-reduction of NAD + and FAD Phosphate of NADP +
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- Last notes on coenzymes The reduced coenzymes, NADH and FADH 2
pick up electrons (in their bonds to hydrogen). These electrons are
passed along in subsequent reactions, they are referred to as
electron carriers. In their reduced forms, they also carry energy
along from reaction to reaction. Ultimately, this energy is passed
on to the bonds in ATP.
- Slide 35
- PART (1): CITRIC ACID CYCLE
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- Acetyl-CoA is a central molecule of metabolism
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- Acetyl-CoA has energy in its bonds The bond between the acetyl
group and the Coenzyme A group carries energy. Hydrolysis of he
acetyl groups in acetyl-SCoA molecules is an energy-releasing
reaction.
- Slide 38
- Citric acid cycle Also known as Krebs cycle or tricarboxylic
acid cycle It describes the oxidation of the 2 carbons of
acetyl-CoA to give and transfer of energy to reduced coenzymes. It
is a cycle because the product of the final step, oxaloacetate is
the reactant in the first step.
- Slide 39
- Summary of the cycle The 2 carbon atoms of the acetyl group add
to the 4 carbon atoms of oxaloacetate in Step 1 2 carbon atoms are
set free as carbon dioxide in Steps 3 and 4. Coenzymes are produced
in four stages (3, 4, 6, and 8) One energy carrier (GTP) is
produced in stage 5 Oxaloacetate is regenerated in stage 8.
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- Where does it happen? The cycle takes place in mitochondria,
where seven of the enzymes are dissolved in the matrix and one (for
Step 6) is embedded in the inner mitochondrial membrane.
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- Slide 42
- Steps 1 and 2 Acetyl groups enter the cycle at Step 1 by
addition to 4-carbon oxaloacetate to give citrate, a 6-carbon
intermediate. Citrate is a tertiary alcohol and cannot be oxidized;
it is converted in Step 2 to its isomer, isocitrate, a secondary
alcohol that can be oxidized to a ketone in Step 3.
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- Steps 3 and 4 Both steps are redox reactions with production of
NADH+ and CO 2. Step 3: The group of isocitrate is simultaneously
oxidized to a keto group. Step 4: succinyl group is added to
coenzyme A.
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- Step 5 The exergonic conversion of succinyl-SCoA to succinate
is coupled with phosphorylation of (GDP) to give (GTP). GTP is an
energy carrier like ATP. GTP can be converted to ATP Step 5 is the
only step in the cycle that generates an energy-rich
triphosphate.
- Slide 45
- STEP 6 Succinate is oxidized to give fumarate. The enzyme for
this reaction, succinate dehydrogenase, is part of the inner
mitochondrial membrane. The reaction requires the coenzyme FAD,
which is covalently bound to its enzyme.
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- Steps 7 and 8 Regeneration of oxaloacetate. Fumarate is
converted to malate, which is a secondary alcohol, that is oxidized
to produce oxaloacetate.
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- Overall reaction Acetyl-CoA + 2H 2 O + 3NAD + + FAD + GDP + P i
2 CO 2 + 3 NADH + FADH 2 + CoASH + GTP + 2H + Production of four
reduced coenzyme molecules (3 NADH + FADH 2 ) Conversion of an
acetyl group to two molecules of CO 2 Production of one energy-rich
molecule (GTP, converted immediately to ATP)
- Slide 48
- Regulation of citric acid cycle Isocitrate dehydrogenase is
activated allosterically by high rate of ADP and allosterically
inhibited by high rate of NADH. -Ketoglutarate dehydrogenase is
inhibited by high levels of ATP and its products (succinyl-CoA and
NADH)
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- PART(3): THE ELECTRON- TRANSPORT CHAIN
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- Electron-transport chain
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- At the conclusion of the citric acid cycle, the reduced
coenzymes formed in the cycle are ready to donate their energy to
making additional ATP. How is it done?
- Slide 52
- Electron-transport chain respiratory chain reaction Electrons
move from one electron carrier to the next. Each carrier becomes
reduced when it gains an electron and then oxidized when it loses
the electron. Each reaction is favorable; that is, it is exergonic,
and energy is stored. This sequence of reactions is known as the
electron- transport chain It is coupled to another process known as
respiratory chain reaction that utilizes the stored energy to
generate ATP.
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- The reactions are sequential and exergonic
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- Where does it take place? The enzymes and coenzymes of the
chain and ATP synthesis are embedded in the inner membrane of the
mitochondrion.
- Slide 55
- Final reaction In the last step of the chain, the electrons
combine with the oxygen and with hydrogen ions from their
surroundings to produce water: The reaction is explosive in nature,
but it is not in biological system. Why?
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- How is energy made? As electrons are transferred, the released
energy is used to move hydrogen ions out of the mitochondrial
matrix and into the intermembrane space. The result is a higher
concentration in the intermembrane space. This energy is recaptured
for use in ATP synthesis by moving hydrogen ions back into the
matrix.
- Slide 57
- Electron transport Electron transport proceeds in four enzyme
complexes located within the inner membrane of mitochondria and two
electron carriers that move from one complex to another. The four
fixed complexes are very large and assembled on polypeptides and
electron acceptors.
- Slide 58
- The electron acceptors Various cytochromes proteins that
contain heme groups in which the iron cycles between and Fe +2 and
Fe +3 Proteins with iron sulfur groups The iron also cycles between
Fe +2 and Fe +3 Coenzyme Q (CoQ) also known as ubiquinone It has a
ring structure with the two ketone groups known as quinone
- Slide 59
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- The steps of electron transport Electrons from NADH enter the
chain at enzyme complex I. Electrons from FADH 2 enter the chain at
enzyme complex II. The enzyme for Step 6 of the citric acid cycle
is part of complex II, so when FADH 2 is produced, it does not
leave complex II and enter the chain immediately. Electrons are
passed from weaker to increasingly stronger oxidizing agents, with
energy released at each transfer. Electrons are carried between the
complexes by two electron carriers: coenzyme Q and cytochrome
c.
- Slide 61
- Gradient of hydrogen ions Hydrogen ions are transported across
the inner membrane from the matrix to the intermembrane space at
complexes I, III, and IV. The concentration difference creates a
potential energy difference across the two sides of the inner
membrane (like the energy difference between water at the top and
bottom of the waterfall).
- Slide 62
- Oxidative phosphorylation The reactions of the
electron-transport chain are tightly coupled to oxidative
phosphorylation The conversion of ADP to ATP by a reaction that is
both an oxidation and a phosphorylation. How is this done?
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- ATP synthase Hydrogen ions can return to the matrix only by
passing through a channel that is part of the ATP synthase enzyme
complex. When they are transported back, they release the potential
energy they gained as they were moved against the concentration
gradient at the enzyme.
- Slide 64
- Synthesis of ATP The energy they release drives the
phosphorylation of ADP by reaction with hydrogen phosphate ion: The
reaction is facilitated by changes in the shape of the enzyme
complex that are induced by the flow of hydrogen ions. As hydrogen
ions flow through the complex, ATP is produced and released back
into the matrix.
- Slide 65
- How much ATP energy is produced? The electrons from NADH
molecules enter the electron-transport chain at complex I, while
those from FADH 2 enter at complex II. These different entry points
into the electron- transport chain result in different yields of
ATP molecules. Each NADH molecule 2.5 molecules of ATP. Make it 3
to simplify. Each molecule of FADH 2 1.5 molecules of ATP. Make it
2 to simplify.
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- Harmful Oxygen By-Products In addition to water, the product of
electron transport chain may be highly reactive species. free
radicals (hydroxyl (HO) and superoxide (O 2 )) and hydrogen
peroxide (H 2 O 2 ) How are they produced?
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- Causes of reactive species The reactivity of the superoxide
free radical is beneficial in destroying infectious microorganisms.
They can break covalent bonds in enzymes and other proteins, DNA,
and the lipids in cell membranes. Among the possible outcomes of
such destruction are cancer, liver damage, rheumatoid arthritis,
heart disease, and immune system damage.
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- How are they removed? Our protection against them is provided
by: Superoxide dismutase Catalase The antioxidant vitamins E, C,
and A (or -carotene) Vitamin C is water-soluble, it is a
free-radical scavenger in the blood.
- Slide 69
- Vitamin E Vitamin E protects cell membranes from potential
damage When a cell membrane lipid (RH) is converted to an oxygen-
containing free radical (ROO. ), vitamin E gives up electrons and
hydrogen atoms to convert the lipid free radical to ROOH, a
peroxide that is then enzymatically converted to ROH.